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GWAS of Heroin Addiction
Introduction Heroin is an opioid drug synthesized from morphine. It is commonly used throughout the United States; in 2011, 4.2 million Americans age 12 years or older admitted to using heroin at least once in their life. It can be addicting, as about 23 percent of individuals who use heroin become dependent on it. Heroin can appear as either white or brown powder or as a black sticky substance. It can be injected, smoked, or inhaled through the nose, however, all three methods deliver the drug to the brain rapidly. Once heroin reaches the brain, it is converted to morphine, which then binds to pain and reward opioid receptors (2). Binding of the morphine molecules produces a downer effect that induces a state of relaxation and euphoria while blocking the ability to perceive pain (3). Genome-Wide Study of Heroin Addiction Some heroin users are more likely to become addicted and dependent than others due to certain genomic factors. To identify which factors were associated with an increase risk of becoming dependent, researchers studied DNA from regular volunteers at The Rockefeller University; 325 of which were former severe heroin addicts and 250 were control individuals. In order to be considered for the study, the volunteers had to meet certain criteria. The former heroin addicts had to meet Federal guidelines for the methadone maintenance treatment, which meant they had to have had one year or more of daily injections of heroin. The control subjects could not have a history of alcohol or illicit drug abuse, they could not use cannabis regularly, and they could not have any alcohol or drug use 30 days before the study. Their DNA was divided into two groups, Caucasian or African-American, to avoid ethnic population stratification errors. The DNA was then analyzed using an Affymetrix GeneChip Mapping 100 K Set, which is a SNP- based genetic mapping tool. Many variants had to be excluded due to low frequency, however, 113,135 Caucasian variants and 113,174 African Americans variants were evaluated (1). Results There were 200 Caucasian and 125 African American former heroin addicts used along with 140 Caucasian and 100 African American controls used for this study. The results show the association with vulnerability to develop a heroin addiction was different depending on race. In Caucasians, a variant rs10494334 in the 1q23.3 unannotated region of the genome showed a strong association with herion addiction. While analyzing the top 500 varients with the most significance, three of the variants were found to be clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. The variant in African Americans that showed a strong association of addiction was rs950302 in the cytosolic dual specificity phosphatase 27 gene DUSP27. While analyzing the top 500 variants in African Americans, three of the most significant variants were found to be located in the cardiomyopathy associated 3 gene CMYA3. This study shows that heroin addiction can be due to not only environmental factors, but genomic factors as well(1). References 1. Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction. Pubmed. 2. Drug Facts: Heroin. National Institute of Drug Abuse. 3. Heroin Addiction: Symptoms and Effects. Timberline Knolls.